Delayed-action genes
Researchers at the University of Cardiff and the Sanger Institute in Cambridge have found that every healthy person is a carrier of about 400 genetic variants that pose a potential threat to health, and 2 variants directly associated with diseases. They demonstrated that 10% of the study participants may develop a genetic disease as a result of the presence of such variants.
For decades, experts have known that the genome of every person contains pathological DNA variants that have little or no effect on health. For the first time, the authors conducted a quantitative assessment of the content of such variants in the genomes of healthy people. To do this, they compared the information contained in two databases: the full-genomic DNA sequences of 179 participants of the pilot "1000 Genomes Project", with a low degree of probability having any obvious manifestations of genetic diseases at the time of sampling for DNA analysis, and a detailed catalog of human mutations associated with diseases described in the scientific literature.
Most likely, the number of potentially dangerous mutations will increase as the effectiveness of methods for studying genetic variants increases. Conducting such work raises ethical issues related to the anonymity of participation in genetic research and accidental findings.
In many cases, pathological or damaged genes were recessive genetic variants, which, in combination with a normal copy of the gene, have no effect on the health of their carrier. The destructive effects of recessive genetic variants are manifested only in the presence of two pathological variants of genes – one on each chromosome of the pair.
However, as it turned out, 1 out of every 10 study participants was a carrier of two recessive pathologically altered copies of the same gene, or a dominant pathological genetic variant. (Dominant are called genetic variants that manifest in the phenotype – in this case, capable of causing symptoms of the disease – if there is even one copy in the genome.) Clinical manifestations of genetic diseases in these people were either poorly expressed or completely absent. The researchers suggested that in the latter case, clinical symptoms may appear at later stages of life.
According to the authors, the results of their work made it obvious that even in the organisms of normal healthy people, many proteins can be represented by abnormal or even completely inactivated forms, without any noticeable damage to health. It is extremely difficult to predict the clinical consequences of the presence of a particular genetic variant in each specific case. The only way to facilitate this task is to further develop databases containing information about genetic variants associated with various diseases. Such bases have begun to appear over the past two decades, but the work on their creation is still far from complete. Pathological genetic variants in general are quite rare and in many populations their search has not yet been practically carried out.
The genetic material used in this study was collected anonymously, so participants cannot receive any information about the risks of developing certain pathologies. Such situations cause researchers more and more concern because of their ethical ambiguity.
The genomes of all people contain errors, however, if potentially dangerous genetic variants in the genomes of some of us are not associated with the risk of developing diseases for one reason or another, their presence in the genomes of other people can have negative consequences. Timely information about such risks can help minimize the consequences, however, on the other hand, it can be a very unpleasant surprise for the participant of the study. Given that DNA sequencing is becoming increasingly widely used, the primary task of geneticists is to develop the most ethical approach to handling confidential information obtained as a result.
Articles by Ali Xue et al. Deleterious- and Disease-Allele Prevention in Healthy Individuals: Insights from Current Predictions, Mutation Databases, and Population-Scale published in the American Journal of Human Genetics.
Evgeniyarabtseva
Portal "Eternal youth" http://vechnayamolodost.ru according to the materials of the Wellcome Trust Sanger Institute:
Researchers produce a catalogue of the deleterious and disease-causing genetic variants in healthy people.
17.12.2012